This proposal is in response to RFA-NS-02-010 Parkinson's Disease Neuroprotective Clinical Trials: Clinical Center. Parkinson's disease is a progressive and debilitating neurodegenerative disorder affecting one-percent of the population overthe age of 55 years. The primary pathological features of PD are the loss of nigrostriatal dopaminergic neurons and subsequent depletion of striatal dopamine. The cause of PD is currently unknown but both environmental and genetic factors may contribute totteetiology of the disease. Since PD is a progressive disease, pharmacological and/or non-pharmacological modalities may be developed to provide neuroprotection through either protecting/rescuing surviving neuronsand slowing disease progression. The primary goal of this proposal is to identify and recruit patients and conduct clinical trials of neuroprotection in early stage PD. An alternative approach to slowing disease progression is by promoting neuroplasticity in surviving nigrostriatal neurons. One possible non-pharmacological intervention is the process of activity-dependent neuroplasticity that may be achieved through long-term exercise (such as treadmill training). The secondary goal of this proposal is to determine if long-term treadmill training attenuatesdisease progression in PDthroughactivity dependent neuroplasticity.